The overall objective of this proposal is to understand why the simiallogeneic fetus is not rejected, which will lead to better understanding of human organ transplantation and tumor rejection. The overall objective will be accomplished by four categories of related projects. The first project will analyze of populations of antibodies produced as a consequence of an allogeneic pregnancy. Specifically, we will determine what populations of antibodies are present or missing against the major epitopes of the paternal class I antigens of the major histocompatibility complex. In addition, we will determine what populations of alloantibodies are detected by the auto-anti-idiotypic antibodies that are also produced as a consequence of some allogeneic pregnancies. The second project will begin analysis of the cell populations that regulate the alloantibody response in the allogeneically pregnant rat. We will determine in what lymphoid cell population resides the absence of memory that occurs in the pregnancy-induced alloantibody response, which is unlike conventional alloimmunizations that always induce memory. The third project begins analysis of the helper T cells that are required to cause the differentiation of cytotoxic lymphocyte (CTL) precursors into CTLs. We will analyze why antipaternal T effector cells are absent in an allogeneic pregnancy. The third project will determine if allogeneic pregnancy sensitizes the T helper cells required for the differentiation of CTL and effector cell precursors. We will also begin an analysis of pregnancy-induced antipaternal DTH because it is likely that DTH effector cells are those that cause graft rejection. The fourth project will determine the amount of fetally-derived paternal antigen that enters the maternal compartment via the uterine vein. This project is being undertaken because most anti-patenal antibody forming cells are found in the spleen and fetectomy prevents the pregnancy-induced alloantibody response. We interpret these data to mean that the antigen that sensitizes the female during pregnancy is of fetal origin and enters the female via the uterine vein. Since we can detect class I antigen in the uterine vein, this means that the amount of antigen entering the female is very large due to the high flow rate in the uterine vein. The regulatory mechanisms that prevent fetal graft rejection may be caused by the large amounts of fetal antigen that enters the pregnant female.